Despite the critical core mechanical stimuli play in hearing, touch, proprioception, blood pressure regulation and the maintenance of osmotic balance, the molecular and cellular basis of these sensory modalities in vertebrates remains elusive. The proposed research used genetic, cellular and molecular techniques in C. elegans to identify receptor proteins, signal transduction pathways and neural circuits involved in mechanosensation and osmosensation in a simple nervous system. The C. elegans ASH sensory neurons respond to nose touch, high osmolarity and volatile chemical repellents. Mutations have been identified which specifically perturb response to nose touch and osmolarity. Yet, these mutations leave intact response to other stimuli detected by ASH. The corresponding proteins are likely to be specifically involved in stimulus detection or reprocessing for each sensory pathway. We will identify additional mutations which specifically perturb nose touch or high osmolarity response. Three modality specific genes will be cloned to understand their role in sensation. Analysis of the osm-10 gene, required by osmosensation, is also proposed. osm-10 encodes a novel protein expressed in four classes of C. elegans sensory neurons, including ASH. Analysis of C. elegans proteins, signal transduction pathways and sensory signal encoding mechanisms is likely to reveal common elements used in stimulus detection and processing in vertebrates.